Antibiotic susceptibility in Endophthalmitis Management Study and intravitreal antibiotic practice trend in India-EMS Report #5.

AIM: Analyze antibiotic susceptibility in the Endophthalmitis Management Study (EMS) and compare it with the current intravitreal antibiotic practice trend of members of the Vitreoretinal Society of India (VRSI) practicing in India. METHODS: The microbiology work-up of undiluted vitreous included microscopy, culture-susceptibility, polymerase chain reaction (PCR), and next-generation sequencing (NGS). VRSI members were invited to the survey. The EMS conventional culture-susceptibility (PCR and NGS excluded) results were compared vis-a-vis gram-positive cocci (GPC), gram-negative bacilli (GNB), and less commonly used antibiotics with the current recommended intravitreal antibiotics. p < 0.05 was considered significant. RESULTS: Culture and positivity (culture + PCR/NGS) positivity was 28.8% and 56.1%, respectively. GPC was most susceptible to cefazolin, linezolid, and vancomycin; GNB was most susceptible to amikacin, ceftazidime, colistin, and imipenem. There was no susceptibility difference between cefazolin and vancomycin (p = 0.999) and between ceftazidime and imipenem (p = 1.0). Colistin was superior to ceftazidime (p = 0.047) against GNB. The GNB resistant to amikacin (n = 14) were equally susceptible to ceftazidime and colistin; resistant to ceftazidime (n = 16) were susceptible to colistin; and resistant to colistin (n = 7) were susceptible to ceftazidime. The preference of VRSI members (n = 231) practicing in India was a vancomycin-ceftazidime combination (82%), vancomycin for GPC (94%), ceftazidime for GNB (61%), and voriconazole for fungi (74%). CONCLUSION: In EMS, GPC had good susceptibility to vancomycin; GNB had good susceptibility to ceftazidime and colistin. Given the lower resistance of colistin, a vancomycin-colistin combination could be an alternative empiric treatment in post-cataract endophthalmitis in India.

Efficacy of an Indian Bevacizumab BIOSimilar (BEVATAS) for Type 1 and Aggressive Posterior Retinopathy of Prematurity (BIOS-ROP Study).

Purpose: To evaluate the role of an Indian bevacizumab biosimilar (Bevatas®), for the management of type 1 retinopathy of prematurity (ROP) and aggressive posterior ROP (APROP) over 24-weeks. Patients and Methods: A retrospective, single-center, interventional study of 144 eyes of type 1 (100 eyes) and APROP (44 eyes). All eyes received a single dose of 0.625mg Bevatas injection, and were advised additional laser therapy for suboptimal response. Results: The study population had a mean gestational age of 28.94 (±2.32) weeks, an average birth weight of 1.2 (±0.34) kg, and modest male predominance (52.05%). Complete regression of ROP was seen in 65.97% of 144 eyes after 24 weeks of bevacizumab monotherapy, and in 97.22% of eyes (140 eyes) after adding laser photocoagulation. The remaining four eyes (all had APROP) developed Stage 4 ROP and needed vitreous surgery. After monotherapy with bevacizumab biosimilar, type 1 ROP eyes had significantly higher rate of complete ROP regression than APROP eyes (87% vs 18.18%; P<0.00001). All eyes with type 1 ROP, and 90.91% of eyes with APROP, regressed after receiving additional laser therapy. The study population experienced no ocular or systemic adverse effects. Conclusion: The BIOS-ROP study demonstrates that intravitreal bevacizumab biosimilar monotherapy offers significant benefit for type 1 ROP, but not APROP. Low-cost biosimilars can help sustain healthcare systems in lower-middle income countries (LMICs) with escalating healthcare expenditures. They can also improve healthcare equity by making vision-saving therapies like bevacizumab more affordable and accessible.

Role of Intravitreal Dexamethasone Implant in the Management of Treatment-Naive Diabetic Macular Edema: A Pre-Cataract Surgical Approach for Patients with Systemic Contraindications to Anti-VEGF Therapy.

Purpose: Diabetic macular edema (DME) is a significant cause of vision impairment, posing challenges in its management due to variable responses and patient diversity. While anti-vascular endothelial growth factor (anti-VEGF) agents have revolutionized DME treatment, some patients are not suitable candidates for this therapy. Intravitreal corticosteroid therapy, such as the dexamethasone implant (DEX), has emerged as an alternative. This study aimed to comprehensively investigate the role of intravitreal DEX in treatment-naive DME patients with systemic contraindications to anti-VEGF therapy, administered one month before cataract surgery. Patients and Methods: A single-center retrospective study included 20 eyes with controlled diabetes, visually significant cataracts, untreated DME, and systemic contraindications for anti-VEGF therapy. Patients underwent DEX treatment followed by cataract surgery after one month. Best-corrected visual acuity (BCVA), central macular thickness (CMT), and intraocular pressure (IOP) were assessed at multiple time points. Results: BCVA significantly improved on days 30, 90, and 180 post-DEX (P<0.00001). CMT showed a significant decrease at day 30 (P<0.00001), which was sustained through days 90 and 180 (P<0.00001). Recurrent DME was observed in 25% of eyes on day 90. IOP increased significantly at days 30 (P<0.00001) and 90 (P=0.0006), returning to baseline by day 180. However, only two eyes needed topical anti-glaucoma treatment. No other ocular or systemic adverse events were noted. Conclusion: Intravitreal DEX administered one month before cataract surgery offers a promising treatment strategy for treatment-naive DME patients with systemic contraindications to anti-VEGF therapy. The study's findings provide insights into improving visual acuity and reducing macular thickness, along with manageable IOP changes. This personalized approach is a valuable addition to DME management, especially for complex medical cases, warranting further research and consideration for clinical practice.

Impact of COVID-19 Pandemic on Retinopathy of Prematurity Services in the Indian Public Healthcare System.

Purpose: To analyze the impact of the COVID-19 pandemic on the retinopathy of prematurity (ROP) services at Special Newborn Care Units (SNCUs), which provide care for sick neonates in the Indian public healthcare system. Methods: A retrospective chart analysis of 508 babies screened for ROP at two SNCUs in West Bengal (India). We compared the data from the lockdown period (April, 2020-June, 2020; study arm) with the same period of the preceding year, 2019 (control arm). Results: Out of the 508 babies, 187 were screened during the lockdown and 328 during 2019. The odds of developing ROP were 2.08 times (95% CI:1.25-3.48; P=0.002) higher during the lockdown period (35/187 babies; 18.72%) as compared to the previous year (34/328 babies; 10.37%). Also, the risk of sight-threatening ROP (ST-ROP) increased significantly during the lockdown (12/35 ROP babies; 34.29%) compared to the previous year (4/34 ROP babies; 11.76%) (odds ratio: 3.9; 95% CI:1.1-13.7; P=0.015). Notably, all babies with ROP during the lockdown presented more than 30 days after birth, compared to none in the previous year. All babies requiring laser therapy recovered completely in both groups. Conclusion: An increased odds of developing ROP, including ST-ROP, was observed during the COVID-19 pandemic. Delayed ROP screening, which was noted in all study eyes, can have a detrimental effect on long-term visual prognosis. The findings of our research call for modifying the present healthy policy framework to make it more adaptable to disruptions in healthcare services, given the cyclical nature of the worldwide COVID-19 pandemic.

Shift Work as a Cardiovascular Disease Risk Factor: A Narrative Review.

Shift work has emerged as a significant health concern in recent years, and research has revealed a link to circadian rhythm dysregulation and atherosclerosis, both of which can increase the risk of cardiovascular disease (CVD). Currently, there is a lack of updated reviews regarding the impact of shiftwork on CVD. Thus, the present narrative review aims to provide a comprehensive summary of the latest research on the relationship between shift work and CVD, identify potential gaps in the current knowledge, and highlight areas for future research. Database searches for peer-reviewed articles published between January 2013 to January 2023 on shift work associated CVD revealed many studies that found shift work is linked with increased prevalence of carotid artery plaque, increased arterial stiffness, and carotid artery intima-media thickness (IMT) all suggestive of a progression of atherosclerosis attributable to shift work. Hypertension, diabetes, and a sedentary lifestyle are known risks for CVD, and the results of the present study suggest that shift work should be added to that list. The elevation of inflammatory markers and DNA damage in shift workers may be linked to their increased progression of atherosclerosis and the positive association of shift work with coronary artery disease. There are minimal studies on mitigating approaches for shift work-related CVD, such as diet modification or exercise, emphasizing the need for further directed research in this area.

Response of extra-large pigment epithelial detachment to intravitreal brolucizumab injection.

Purpose: To determine the role of intravitreal injection (IVI) of brolucizumab for extra-large pigment epithelial detachment (PED) secondary to macular neovascularization (MNV). Observations: A prospective, non-randomized, uncontrolled case series of three eyes of three patients with extra-large PED (maximum height >350 µm) due to untreated MNV was undertaken at a single center. All three eyes showed significant improvement in the PED height by week 4, with complete resolution by week 8 in two of the three. The third patient who received the second dose is scheduled for a follow-up. Simultaneous notable visual improvement was also observed in all of the eyes. Furthermore, there were no ocular or systemic safety concerns in any of the cases. Conclusions and Importance: Our real-world case series indicates that intravitreal brolucizumab is efficacious and safe for the management of extra-large PEDs in treatment-naïve MNV eyes. To better understand brolucizumab's mechanism of action, particularly at the sub-RPE and choroidal levels, and the underlying functional principle for the PED response, more study of the drug's pharmacotherapeutics is warranted.

Management of Submacular Hemorrhage Using Intravitreal Brolucizumab with Pneumatic Displacement: A Case Series.

The management of submacular hemorrhage (SMH) necessitates rapid clearing of the bleed for optimal visual outcomes. We present a series of 3 cases with large fresh SMH (≤7 days) secondary to MNV that were treated with intravitreal injection (IVI) of brolucizumab along with SF6 gas injection. A face-down position was recommended for 5 days after the injection, with follow-up visits at regular intervals. All eyes demonstrated notable improvement in visual acuity with complete resolution of SMH lasting up to 6 months. There were no ocular or systemic side effects. Thus, IVI brolucizumab with SF6 gas injection is efficacious and safe for the management of large SMH secondary to MNV.

Brolucizumab in Neovascular Age-Related Macular Degeneration - Indian Real-World Experience: The BRAILLE Study - Fifty-Two-Week Outcomes.

Purpose: To report the 52-week real-world efficacy and safety outcomes of brolucizumab therapy for neovascular age-related macular degeneration (nAMD) in Indian eyes. Patients and Methods: A retrospective, multicentre chart analysis of 82 eyes of 82 patients with nAMD (switch therapy: 65 eyes; treatment-naïve: 17 eyes) with 52-week follow-up data was performed. Pro-re-nata re-treatment was offered based on visual and tomographic criteria. Changes in best-corrected visual acuity (BCVA), intraretinal fluid (IRF), subretinal fluid (SRF), central-subfield thickness (CST), and pigment epithelial detachment (PED) were the key outcome measures, coupled with the safety profile. Results: The mean age of the study population was 67.65 (±10.67) years, with 57 male patients (69.5%). The study's mean number of injections was 4.8 (± 0.77). After brolucizumab therapy, the BCVA improved significantly at weeks 4 (P<0.001), and maintained up to week 52 (P<0.001). The CST also reduced significantly at all the visits (Baseline: 413.6 ± 64.6 µm; 52-week: 292.37 ± 13.5 µm; P<0.001). Significantly fewer eyes demonstrated residual SRF (P<0.001) and IRF (P<0.001) at all visits, starting with week 12 and continuing until week 52. The PED resolution was significant from week 24 through week 52 (P=0.004). Each of the 82 eyes received four injections of brolucizumab, with 63.4% (52 eyes) receiving a fifth dose and only 17.1% requiring a sixth. Mild intraocular inflammation (IOI) was seen in three eyes (3.66%) that resolved conservatively. One patient (1.2%) developed mild fever that subsided with oral medications. Conclusion: The 52-week BRAILLE study demonstrates that brolucizumab is effective and safe in nAMD eyes in a real-world setting. Brolucizumab treatment can reduce the therapeutic burden in patients with nAMD due to its rapid, sustained efficacy and favourable safety profile.

Rapid Onset Neovascular Glaucoma due to COVID-19-related Retinopathy.

Aim: To present a case of rapid onset on neovascular glaucoma following the Coronavirus disease 2019 (COVID-19). Background: COVID-19 has various ocular manifestations such as conjunctivitis, uveitis, retinal vasculitis, and so on. However, to date, the development of neovascular glaucoma has not been reported in COVID-19. Case description: A 50-year-old male with a history of COVID-19 3 weeks ago presented with left eye (OS) central retinal artery occlusion (CRAO) and right eye (OD) cystoid macular edema with disc and microvascular leakage on multimodal imaging. After being managed conservatively for 2 weeks, the patient developed OD neovascular glaucoma with intraocular pressure (IOP) of 44 mm Hg and angle neovascularization (NVA) on gonioscopy. The patient was started on topical antiglaucoma medications (AGM) with panretinal photocoagulation (PRP) and responded well with complete regression of NVA, CME, and normal IOP after 3 weeks. Conclusion: This is the first reported case of rapid onset of NVG secondary to COVID-19-induced retinal vasculitis. COVID-19-associated prothrombotic state with secondary retinal vascular involvement can potentially trigger such NVG. Such NVG responds well with topical AGM and PRP therapy. Clinical significance: Given the global COVID-19 pandemic, it is imperative to be vigilant regarding the various vision-threatening manifestations associated with the disease such as the NVG. How to cite this article: Soman M, Indurkar A, George T, et al. Rapid onset Neovascular Glaucoma due to COVID-19-related Retinopathy. J Curr Glaucoma Pract 2022;16(2):136-140.

Updated guidelines for the management of polypoidal choroidal vasculopathy: Recommendations from the Indian Polypoidal Choroidal Vasculopathy Panel and the Vitreoretinal Society of India.

In Asians, polypoidal choroidal vasculopathy (PCV) is becoming more widely recognized as a significant cause of exudative maculopathy. The previous set of Indian guidelines on the management of PCV were published in 2018, with a literature search updated up to November 2015. As the treatment of PCV evolves, retinal physicians must constantly modify their current practice. The current guidelines are based on the most up-to-date information on PCV and are an update to the previous set of guidelines. These guidelines were developed by a panel of Indian retinal experts under the aegis of the Vitreoretinal Society of India (VRSI), based on a comprehensive search and assessment of literature up to September 2021. The final guidelines i) provide the updated nomenclature in PCV; ii) discusses the newer diagnostic imaging features of PCV, especially in the absence of indocyanine green angiography (ICGA); and iii) recommends the best possible therapeutic approach in the management of PCV, including the choice of anti-vascular endothelial growth factor (anti-VEGF) agents, treatment regimen, and the role of switching between the anti-VEGF agents. In the face of non-availability of photodynamic therapy (PDT) in India, we constructed practical recommendations on anti-VEGF monotherapy in PCV. The current updated recommendations would provide a broader framework to the treating retinal physician for the diagnosis and management of PCV for optimal therapeutic outcomes.

Intravitreal Brolucizumab for Choroidal Neovascularization Associated to Angioid Streaks.

A 44-year-old-female with angioid streak- (AS-) associated choroidal-neovascularization (CNV) was treated with one dose of intravitreal brolucizumab (IB). At one-month, the patient's visual acuity (VA) improved from 20/120 to 20/40 with a dry macula on spectral-domain optical-coherence tomography (SD-OCT). After observation, the VA improved further to 20/32 with absence of any fluid on the SD-OCT at three months. No ocular or systemic adverse events were noted. In conclusion, intravitreal brolucizumab (IB) is an efficacious and safe therapeutic option for the management of CNV secondary to AS. Further prospective studies with a larger sample size, varied therapeutic regimens, and longer follow-up period are needed to corroborate our findings.

COVID-Kavach-Based Seropositivity in the General Population of Ahmedabad: Just Before the Start of the Vaccination for the Elderly in India.

Background The present study was carried out in succession of three serosurvey studies carried out during 2020 in Ahmedabad with an objective to estimate the seroprevalence of immunoglobulin G (IgG) antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) in Ahmedabad city so as to scientifically understand the pandemic progression. Methods Polio booth-based stratification was followed for the population-based stratified sampling among the general population of Ahmedabad. The seroprevalence was compared with various factors for valid and precise predictions regarding the immunity status of the population. Results As on February 2021, the seroprevalence for IgG antibodies against SARS-CoV2 in the general population of Ahmedabad was 27.92% (95% confidence interval 27.06-28.80), much below the minimum desired for herd immunity. Comparison of seropositivity with age groups showed higher seroprevalence with increasing age groups. Seroprevalence was higher among males (29.08%) than females (27.01%) and the difference was statistically significant (Z=2.30, P=0.02). Calculating the seropositivity among the subcategories, cases had a seropositivity of 64.90% and family contacts had a seropositivity of 28.00%. Seronegative cases indicate the possibility of absent, undetectable, or disappearing IgG antibodies. Seropositivity of 37% among the vaccinated individuals may be related to dose and duration of vaccination, as the COVID vaccination had started just before the present study and none had completed 14 days after the second dose. Conclusions The low level of IgG antibodies against SARS-CoV2 using the COVID-Kavach test kit in the general population of Ahmedabad city of India, as on February 2021, before the start of COVID vaccination for the general population suggests that the preventive measures be strongly followed for continued control of the pandemic situation at least till majority of the population is effectively covered with vaccination.

Innovator Versus Biosimilar Ranibizumab in Polypoidal Choroidal Vasculopathy: Real-World Evidence.

INTRODUCTION: To analyze the efficacy and safety profile of the intravitreal ranibizumab biosimilar molecule, Razumab® (Intas Pharmaceuticals, Ahmedabad, India; BRm; Razumab®) and the innovator ranibizumab drug (IRm; LUCENTIS®) in Indian patients with polypoidal choroidal vasculopathy (PCV) under real-world conditions. METHODS: This was a retrospective study of treatment-naïve and previously treated PCV eyes undergoing intravitreal therapy with either BRm or IRm from January 2019 to September 2020 as three loading doses followed by a pro-re-nata (PRN) regimen. Changes in the best-corrected visual acuity (BCVA), subretinal fluid (SRF), intraretinal fluid (IRF), SRF height, and subfoveal choroidal thickness (SFCT) and the safety profiles were assessed at weeks 12, 24, and 52, respectively. RESULTS: A total of 22 eyes received IRm and 19 eyes underwent BRm therapy, respectively. Both the groups were comparable in age (P = 0.41) and gender distribution, although the BRm arm had significantly more eyes that were previously treated (P < 0.00001) with a greater median number of injections (P < 0.0001). At week 52, both groups had similar gains in visual acuity (P = 0.19), SRF resolution (P = 0.8), IRF resolution (P = 0.47), and SRF height (P = 0.71). The IRm eyes exhibited a significant improvement in BCVA (P = 0.001) at all visits with a greater mean number of injections (IRm: 5.41 ± 0.94; BRm: 4 ± 1.45; P = 0.0004), while the BRm eyes showed a similar increase in BCVA but did not reach statistical significance until week 52. The SFCT decreased significantly in the BRm arm at week 52 (P = 0.045). One eye (5.26%) in the BRm arm experienced mild anterior uveitis, which was treated with topical corticosteroids. In either arm, no other ocular or systemic adverse effects were observed. CONCLUSIONS: Our real-world data demonstrated the ranibizumab biosimilar Razumab to have comparable visual acuity outcomes to the innovator ranibizumab molecule with an adequate safety profile in the management of PCV. Although these encouraging results support its use as a viable alternative to the innovator molecule, further prospective studies in a diverse patient population are needed to validate our findings.

Immunoglobulin-G Antibodies against Severe Acute Respiratory Syndrome - Coronavirus-2 among Health-Care Workers: A Serosurveillance Study from India.

Background: Seropositivity among health-care workers (HCWs) may help in better understanding of the immune response after COVID-19 infection. Objectives: To estimate seropositivity among HCWs and to compare available variables with seropositivity to understand the factors affecting seropositivity. Materials and Methods: A serosurveillance among HCWs was carried out using population proportion sampling during the second half of October 2020 in the city of Ahmedabad using the Covid-Kavach (immunoglobulin G [IgG] ELISA Antibody testing kit). Simple proportions and appropriate statistical tests were used as needed. Results: As on October' 2020, HCWs in Ahmedabad demonstrated a seropositivity of 20.84% (95% confidence interval [CI] 19.00-22.81%). Seropositivity among HCWs was lower than that of the general population (24.20%) which was estimated as part of the same study. Female HCWs had higher seropositivity 22.14% (95% CI 19.74-24.74%) as compared to 18.82% (95% CI 16.06-21.93%) among male HCWs and the difference was statistically not significant (Z = 1.66, P = 0.097). Age groups with increasing age show increasing trend in the seropositivity among HCWs. Conclusion: As on October 2020, with 20.84% seropositivity among HCWs in Ahmedabad, one in every five HCW already demonstrate IgG antibodies against severe acute respiratory syndrome- coronavirus-2. Further scientific studies on seropositivity and the factors affecting the seropositivity may be carried out to uncover more details of immune reaction after COVID-19 infection.

Contralateral Effect following Intravitreal Brolucizumab Injection in Diabetic Macular Edema.

The authors describe a novel case of a 48-year-old male with bilateral diabetic macular edema (DME) who underwent intravitreal injection (IVI) of brolucizumab in the left eye. At four weeks, the patient demonstrated a bilateral response by way of improvement in the best-corrected visual acuity (BCVA) and reduction in the central macular thickness (CMT) in both eyes. Further studies on the ocular and systemic assays of the brolucizumab molecule are warranted to evaluate its systemic escape and to better understand the pharmacokinetics behind the bilateral effect.

Role of intravitreal brolucizumab with intravitreal rtPA and pneumatic displacement for submacular hemorrhage: A case series.

PURPOSE: To evaluate the role of intravitreal injection (IVI) of brolucizumab along with intravitreal recombinant tissue plasminogen activator (rtPA) and C3F8 gas injection for large submacular hemorrhage (SMH) secondary to neovascular age-related macular degeneration (nAMD). OBSERVATIONS: This was a prospective uncontrolled non-randomized case series conducted at a single site. Three patients with fresh SMH (≤4 days) secondary to nAMD underwent triple therapy with IVI brolucizumab + intravitreal rtPA (50 µg in 0.1 mL) + 0.3 mL of 100% C3F8 gas injection. Post-injection, a face-down position was advised for 5 days with periodic follow-up visits. All three patients had complete resolution of SMH at the end of 4 weeks with a notable improvement in the best-corrected visual acuity (BCVA). No optical coherence tomographic (OCT) biomarkers of disease activity were noted at the end of 12 weeks in the first and the third case and 4 weeks in the second case respectively. There were no ocular or systemic side effects reported in any of the cases. CONCLUSIONS AND IMPORTANCE: Intravitreal brolucizumab administered along with intravitreal rtPA and C3F8 gas injection was found to be efficacious and safe for the management of large SMH secondary to nAMD. Complete displacement of SMH with excellent structural and functional outcomes can be seen with triple therapy.